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Nano Letters Mar 2018Various delivery vectors have been integrated within biologically derived membrane systems to extend their residential time and reduce their reticuloendothelial system...
Various delivery vectors have been integrated within biologically derived membrane systems to extend their residential time and reduce their reticuloendothelial system (RES) clearance during systemic circulation. However, rational design is still needed to further improve the in situ penetration efficiency of chemo-drug-loaded membrane delivery-system formulations and their release profiles at the tumor site. Here, a macrophage-membrane-coated nanoparticle is developed for tumor-targeted chemotherapy delivery with a controlled release profile in response to tumor microenvironment stimuli. Upon fulfilling its mission of tumor homing and RES evasion, the macrophage-membrane coating can be shed via morphological changes driven by extracellular microenvironment stimuli. The nanoparticles discharged from the outer membrane coating show penetration efficiency enhanced by their size advantage and surface modifications. After internalization by the tumor cells, the loaded drug is quickly released from the nanoparticles in response to the endosome pH. The designed macrophage-membrane-coated nanoparticle (cskc-PPiP/PTX@Ma) exhibits an enhanced therapeutic effect inherited from both membrane-derived tumor homing and step-by-step controlled drug release. Thus, the combination of a biomimetic cell membrane and a cascade-responsive polymeric nanoparticle embodies an effective drug delivery system tailored to the tumor microenvironment.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biomimetic Materials; Breast Neoplasms; Cell Line, Tumor; Cell Membrane; Delayed-Action Preparations; Drug Delivery Systems; Female; Humans; Macrophages; Mice; Nanoparticles; Paclitaxel; Tumor Microenvironment
PubMed: 29473753
DOI: 10.1021/acs.nanolett.7b05263 -
Cell Mar 2024Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG...
Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.
Topics: Animals; Mice; Ganglia, Spinal; Sensory Receptor Cells; Single-Cell Gene Expression Analysis; Skin
PubMed: 38442711
DOI: 10.1016/j.cell.2024.02.006 -
Archives of Pathology & Laboratory... Mar 2007Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3... (Review)
Review
CONTEXT
Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification.
OBJECTIVE
To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas.
DATA SOURCES
Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed.
CONCLUSIONS
Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Gliosarcoma; Humans; Oligodendroglioma
PubMed: 17516742
DOI: 10.5858/2007-131-397-G -
Sports Medicine - Open Dec 2015The present article systematically reviews recent literature on the in vivo adaptation of asymptomatic human tendons following increased chronic mechanical loading, and... (Review)
Review
BACKGROUND
The present article systematically reviews recent literature on the in vivo adaptation of asymptomatic human tendons following increased chronic mechanical loading, and meta-analyzes the loading conditions, intervention outcomes, as well as methodological aspects.
METHODS
The search was performed in the databases PubMed, Web of Knowledge, and Scopus as well as in the reference lists of the eligible articles. A study was included if it conducted (a) a longitudinal exercise intervention (≥8 weeks) on (b) healthy humans (18 to 50 years), (c) investigating the effects on mechanical (i.e., stiffness), material (i.e., Young's modulus) and/or morphological properties (i.e., cross-sectional area (CSA)) of tendons in vivo, and was reported (d) in English language. Weighted average effect sizes (SMD, random-effects) and heterogeneity (Q and I statistics) of the intervention-induced changes of tendon stiffness, Young's modulus, and CSA were calculated. A subgroup analysis was conducted regarding the applied loading intensity, muscle contraction type, and intervention duration. Further, the methodological study quality and the risk of bias were assessed.
RESULTS
The review process yielded 27 studies with 37 separate interventions on either the Achilles or patellar tendon (264 participants). SMD was 0.70 (confidence interval: 0.51, 0.88) for tendon stiffness (N=37), 0.69 (0.36, 1.03) for Young's modulus (N=17), and 0.24 (0.07, 0.42) for CSA (N=33), with significant overall intervention effects (p<0.05). The heterogeneity analysis (stiffness: I =30%; Young's modulus: I =57%; CSA: I =21%) indicated that differences in the loading conditions may affect the adaptive responses. The subgroup analysis confirmed that stiffness adaptation significantly (p<0.05) depends on loading intensity (I =0%), but not on muscle contraction type. Although not significantly different, SMD was higher for interventions with longer duration (≥12 weeks). The average score of 71±9% in methodological quality assessment indicated an appropriate quality of most studies.
CONCLUSIONS
The present meta-analysis provides elaborate statistical evidence that tendons are highly responsive to diverse loading regimens. However, the data strongly suggests that loading magnitude in particular plays a key role for tendon adaptation in contrast to muscle contraction type. Furthermore, intervention-induced changes in tendon stiffness seem to be more attributed to adaptations of the material rather than morphological properties.
PubMed: 27747846
DOI: 10.1186/s40798-015-0009-9 -
BioRxiv : the Preprint Server For... Apr 2023Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG)....
Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.
PubMed: 37131664
DOI: 10.1101/2023.04.22.537932 -
Science Advances May 2022The healthy functioning of the plants' vasculature depends on their ability to respond to environmental changes. In contrast, synthetic microfluidic systems have rarely...
The healthy functioning of the plants' vasculature depends on their ability to respond to environmental changes. In contrast, synthetic microfluidic systems have rarely demonstrated this environmental responsiveness. Plants respond to environmental stimuli through nastic movement, which inspires us to introduce transformable microfluidics: By embedding stimuli-responsive materials, the microfluidic device can respond to temperature, humidity, and light irradiance. Furthermore, by designing a foldable geometry, these responsive movements can follow the preset origami transformation. We term this device TransfOrigami microfluidics (TOM) to highlight the close connection between its transformation and the origami structure. TOM can be used as an environmentally adaptive photomicroreactor. It senses the environmental stimuli and feeds them back positively into photosynthetic conversion through morphological transformation. The principle behind this morphable microsystem can potentially be extended to applications that require responsiveness between the environment and the devices, such as dynamic artificial vascular networks and shape-adaptive flexible electronics.
PubMed: 35507654
DOI: 10.1126/sciadv.abo1719 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2020The ultimate goal of treatment for acute myeloid leukemia (AML) is to improve survival, and the best means of doing so is through the induction of morphologic remission,... (Review)
Review
The ultimate goal of treatment for acute myeloid leukemia (AML) is to improve survival, and the best means of doing so is through the induction of morphologic remission, which is historically most reliably achieved with intensive chemotherapy regimens. Older patients with AML are less likely to be candidates for or to benefit from intensive chemotherapy. Patients deemed ineligible for intensive therapy may nevertheless benefit from lower-intensity therapies and from newly available targeted AML treatments. Recently approved lower-intensity treatments for AML include enasidenib, ivosidenib, glasdegib, venetoclax, midostaurin, and gilteritinib, and additional promising agents are in later stages of clinical development. Noncytotoxic agents may result in slower kinetics of therapeutic activity compared to intensive regimens, and although they are generally better tolerated than intensive chemotherapy, bone marrow responses are less frequent and may take longer to achieve. Notably, newer therapies might have been considered ineffective had they been judged solely by 2003 International Working Group response criteria for AML, which were based on experience with intensive regimens in predominantly younger patients. Lower-intensity therapies may require several treatment cycles to induce responses, and failure to achieve rapid morphologic remission may not signal the need for treatment cessation or transition to alternative therapies. Additionally, even in the absence of a conventional complete remission, lower-intensity therapies may provide meaningful clinical benefit, including improved survival and quality of life, by inducing hematologic improvement and transfusion independence. Reviewed here are the mechanisms of activity and response kinetics of lower-intensity AML therapies, as well as the clinical benefits resulting from nontraditional AML responses.
Topics: Aged; Humans; Kinetics; Leukemia, Myeloid, Acute
PubMed: 31862181
DOI: 10.1016/j.clml.2019.11.017 -
Blood Reviews Sep 2018The International Working Group (IWG) response criteria for acute myeloid leukemia, published in 2003, have remained the standard by which the efficacy of new drugs is... (Review)
Review
The International Working Group (IWG) response criteria for acute myeloid leukemia, published in 2003, have remained the standard by which the efficacy of new drugs is measured in clinical trials. Over the last decade, concepts related to treatment response have been challenged by several factors; for example, the dissociation between early clinical response and survival outcome in older patients, the recognition that epigenetic and newer differentiating-agent therapies may produce delayed responses and also hematologic improvement/transfusion independence without a morphologic response, and evidence that remissions without minimal (or measurable) residual disease (MRD) may result in outcomes superior to those of morphologic remissions with persistent MRD. The evolving role of MRD status as a potential surrogate for predicting long-term survival has enhanced the clinical need to standardize and incorporate emerging technologies that enable deeper responses beyond those recognized by the IWG, and to pre-emptively identify patients at risk of early relapse. The potential for therapeutic interventions to erase MRD and alter the natural history represents an important and open research question. Reviewed here are some of the implications and challenges associated with establishing and incorporating new treatment response criteria, initially into clinical research, and eventually into real-world practice.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Humans; Leukemia, Myeloid, Acute; Neoplasm, Residual; Prognosis; Remission Induction; Treatment Outcome
PubMed: 29706486
DOI: 10.1016/j.blre.2018.03.006 -
International Journal of Molecular... Nov 2021Drought stress causes changes in the morphological, physiological, biochemical and molecular characteristics of plants. The response to drought in different plants may... (Review)
Review
Drought stress causes changes in the morphological, physiological, biochemical and molecular characteristics of plants. The response to drought in different plants may vary from avoidance, tolerance and escape to recovery from stress. This response is genetically programmed and regulated in a very complex yet synchronized manner. The crucial genetic regulations mediated by non-coding RNAs (ncRNAs) have emerged as game-changers in modulating the plant responses to drought and other abiotic stresses. The ncRNAs interact with their targets to form potentially subtle regulatory networks that control multiple genes to determine the overall response of plants. Many long and small drought-responsive ncRNAs have been identified and characterized in different plant varieties. The miRNA-based research is better documented, while lncRNA and transposon-derived RNAs are relatively new, and their cellular role is beginning to be understood. In this review, we have compiled the information on the categorization of non-coding RNAs based on their biogenesis and function. We also discuss the available literature on the role of long and small non-coding RNAs in mitigating drought stress in plants.
Topics: Droughts; Gene Expression Regulation, Plant; MicroRNAs; Plant Development; Plants; RNA, Long Noncoding; RNA, Untranslated; Stress, Physiological
PubMed: 34830399
DOI: 10.3390/ijms222212519 -
Biomarker Research Jul 2021Response Evaluation Criteria in Solid Tumors (RECIST) is the gold standard for assessment of treatment response in solid tumors. Morphologic change of tumor size... (Review)
Review
Response Evaluation Criteria in Solid Tumors (RECIST) is the gold standard for assessment of treatment response in solid tumors. Morphologic change of tumor size evaluated by RECIST is often correlated with survival length and has been considered as a surrogate endpoint of therapeutic efficacy. However, the detection of morphologic change alone may not be sufficient for assessing response to new anti-cancer medication in all solid tumors. During the past fifteen years, several molecular-targeted therapies and immunotherapies have emerged in cancer treatment which work by disrupting signaling pathways and inhibited cell growth. Tumor necrosis or lack of tumor progression is associated with a good therapeutic response even in the absence of tumor shrinkage. Therefore, the use of unmodified RECIST criteria to estimate morphological changes of tumor alone may not be sufficient to estimate tumor response for these new anti-cancer drugs. Several studies have reported the low reliability of RECIST in evaluating treatment response in different tumors such as hepatocellular carcinoma, lung cancer, prostate cancer, brain glioma, bone metastasis, and lymphoma. There is an increased need for new medical imaging biomarkers, considering the changes in tumor viability, metabolic activity, and attenuation, which are related to early tumor response. Promising imaging techniques, beyond RECIST, include dynamic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), diffusion-weight imaging (DWI), magnetic resonance spectroscopy (MRS), and F-fluorodeoxyglucose (FDG) positron emission tomography (PET). This review outlines the current RECIST with their limitations and the new emerging concepts of imaging biomarkers in oncology.
PubMed: 34215324
DOI: 10.1186/s40364-021-00306-8